Objective To investigate the relationship between pre-liver transplantation plasma soluble programmed cell death protein 1 (sPD-1) levels and prognosis in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICI). Methods A total of 38 HCC liver transplant recipients who received ICI treatment at Beijing Tsinghua Changgung Hospital from January 2021 to February 2024 were included in the study. The use of ICI drugs was reviewed, and the clinical and pathological characteristics of patients with and without postoperative HCC recurrence were compared. Kaplan-Meier analysis was used to evaluate postoperative survival. Pre-transplant plasma samples were collected from patients treated with ICI, and the sPD-1 levels were measured using enzyme-linked immunosorbent assay. Receiver operating characteristic curves were plotted to explore the relationship between sPD-1 expression and clinical pathological features and to analyze the prognosis. The effects of different preoperative ICI discontinuation times on sPD-1 expression were also compared. Results Among the patients, 28 (74%) received anti-programmed cell death protein 1 (PD-1) monoclonal antibodies, 9 (24%) received anti-programmed cell death protein ligand 1 (PD-L1) monoclonal antibodies, and 1 (3%) received bispecific antibodies. Patients were grouped based on whether they had HCC recurrence within 1 year after surgery. Significant differences were found between the two groups in preoperative alpha-fetoprotein levels, tumor number, maximum tumor diameter, capsular invasion, differentiation grade, Ki67 index, conform to Milan criteria, conform to University of California at San Francisco (UCSF) criteria and tumor, node, metastasis (TNM) staging (all P<0.05). The median pre-transplant plasma sPD-1 level was 902 (318, 4 406) pg/mL, and the sPD-1 level was higher in the recurrence group than in the non-recurrence group (P<0.05). Using 2 073 pg/mL as the cut-off value, patients were divided into high and low sPD-1 level groups. Significant differences were found between the two groups in tumor number, postoperative hospital stay and total hospital stay (all P<0.05). Kaplan-Meier analysis showed that the disease-free survival rate was lower in the high sPD-1 level group than in the low sPD-1 level group (P=0.004), while the overall survival rate did not differ significantly between the two groups (P=0.381). In addition, patients who discontinued ICI treatment ≤ 5 half-lives before surgery had higher sPD-1 levels than those who discontinued ICI treatment for >5 half-lives before surgery. Conclusions Pre-transplant plasma sPD-1 levels are closely related to prognosis and may reflect the dynamic changes in the immune microenvironment. For patients with high pre-transplant plasma sPD-1 levels, the indications for liver transplantation should be carefully evaluated, and postoperative management and follow-up should be strengthened. Early intervention should be provided to improve patients' quality of life and prolong their survival.

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

The establishment of mouse models is critical for discovering the biological targets of tumorigenesis and cancer development, preclinical trials of targeted drugs, and formulation of personalized therapeutic regimens. Currently, the patient-derived xenograft (PDX) model is considered a reliable animal tumor model because of its ability to retain the characteristics of the primary tumor at the histopathological, molecular, and genetic levels, and to preserve the tumor microenvironment. The application of the PDX model has promoted in-depth research on tumors in recent years, focusing on drug development, tumor target discovery, and precise treatment of patients. However, there are still some common questions. This review introduces the latest research progress and common questions regarding tumors with high mortality rates, focusing on their application in targeted drug screening and the formulation of personalized medical strategies. The challenges faced, improvement methods, and future development of the PDX model in tumor treatment applications are also discussed. This article provides technical guidance and comprehensive expectations for anti-cancer drug screening and clinical personalized therapy.

Shiwei-Ruxiang-capsule (SWRXC) is a classic formulation widely used in the treatment of rheumatoid arthritis (RA). The study used liquid chromatography-tandem mass spectrometry (LC-MS/MS) serum untargeted metabolomics and high-throughput 16S rRNA gene sequencing association analysis to elucidate the mechanism of action of SWRXC for the treatment of Freund's complete adjuvant-induced RA. The results showed that SWRXC significantly improved symptoms and reduced serum cytokine levels in RA rats. Based on LC-MS/MS technology, metabolomics identified tryptophan metabolism, nucleotide metabolism and purine metabolism as the most relevant pathways for treatment. In addition, 16S rRNA sequencing results showed that SWRXC could ameliorate RA-induced intestinal microbial oncogenesis in rats. In conclusion, SWRXC can improve the morphology and structure of RA joint tissues, reduce serum factor levels, and may play a role in improving RA by modulating related metabolic pathways such as tryptophan metabolism, nucleotide metabolism and purine metabolism, and altering the composition of intestinal flora. Animal protocols were approved by the Animal Ethics Committee of Qinghai Normal University (No. 2021041203).

Objective To analyze the expression of cyclooxygenase-2 (COX-2) in the patients with snow-white sign of advanced colorectal adenoma (ACA) and explore its clinical significance.Method Western blotting was employed to determine the expression of COX-2 in the adenoma tissue and the normal tissue adjacent to the adenoma tissue (>5 cm away from the distal end of the adenoma tissue) of 40 ACA patients with snow-white sign and 40 ACA patients without snow-white sign.Results The appearance of snow-white sign in ACA patients was associated with patient age (P=0.001) and not associated with sex,smoking history,drinking history,ethnic groups,family history of colorectal cancer,abdominal pain,diarrhea,constipation,fecal occult blood,or tumor markers (all P>0.05).Snow-white sign mainly appeared in the ACA patients with multiple adenomas (P=0.004),large adenomas (P=0.006),adenomas in distal colon (P=0.015),protruding polyps (P=0.044),and late-stage pathology (P=0.010).The occurrence of snow-white sign showed no difference in the ACA patients with different results of Japan NBI Expert Team classification (P=0.502).The expression of COX-2 in the adenoma tissue was higher than that in the adjacent normal tissue in the patients with and without snow-white sign (P<0.001,P=0.004).The patients with snow-white sign had higher expression of COX-2 protein in the adenoma tissue than the patients without snow-white sign (P=0.001).The expression of COX-2 protein in the adjacent healthy tissue had no significant difference between the patients with and without snow-white sign (P=0.603).Conclusions Snow-white sign is more like to appear in the ACA patients with young age,multiple and large adenomas,adenomas in distal colon,protruding polyps,and late-stage pathology.Moreover,the expression of COX-2 in the ACA patients with snow-white sign is significantly higher than that in the ACA patients without snow-white sign.The adults with snow-white sign are prone to cancerization than those without snow-white sign.
Adult ; Humans ; Cyclooxygenase 2 ; Snow ; Colorectal Neoplasms ; Adenoma

Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy characterized by simple operation and few postoperative complications have gradually become the two most commonly used surgical methods in clinical practice.A series of complications often occur after bariatric surgery,including gallstone disease,anemia,malnutrition,gastroesophageal reflux disease,kidney stones,and birth defects in offspring of women of childbearing age.There are controversies regarding the causes and countermeasures of these complications.This article mainly reviews the risk factors and countermeasures for the complications after bariatric surgery.
Humans ; Female ; Bariatric Surgery/methods* ; Gastric Bypass/methods* ; Gastroesophageal Reflux/surgery* ; Postoperative Complications/prevention & control* ; Risk Factors ; Gastrectomy/methods* ; Laparoscopy/methods* ; Obesity, Morbid/surgery* ; Retrospective Studies

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.
Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China/epidemiology* ; Diseases in Twins/genetics* ; Hyperlipidemias/genetics* ; Metabolic Diseases ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

Subepithelial connective tissue or free gingival grafts are often used in traditional mucogingival surgery to treat gingival recession and keratinized gingival insufficiency. However, due to the disadvantages of autologous soft tissue grafts, such as the preparation of the second surgical site, the limited amount of tissue in the donor site, and postoperative discomfort for patients, the research on autologous soft tissue substitute materials has attracted extensive attention. A variety of donor-substitute materials from different sources are currently used in membranous gingival surgeries, including platelet-rich fibrin, acellular dermal matrix, xenogeneic collagen matrix, etc. This paper reviews the research progress and application of several different types of substitute materials in soft tissue augmentation for natural teeth, providing a reference for the application of autologous soft tissue substitutes in clinical gingival augmentation surgery.